Children and adolescents meeting DSM-III-R criteria for schizophrenia are available and eleven subjects have participated to date in this study of the phenomenology, neurobiology and pharmacologic response of childhood onset schizophrenia. Diagnostic reliability has been established. One hundred fifty children and adolescents with a clinical diagnosis of schizophrenia have been screened by medical records and 46 patients, appearing to meet DSM-III-R criteria for schizophrenia with medical record history of onset of psychosis prior to age twelve were interviewed personally. At least three subgroups of DSM-III-R diagnosed schizophrenic children have been hypothesized based on differences in clinical phenomenology. Pilot family/genetic data indicate one case is familial and a second subject had a chromosomal aberration. Autonomic measures parallel adult schizophrenia MRI abnormalities have been found in the brainstem and [18] fluro-2-deoxy-D-glucose (FDG) PET scanning indicates decreased metabolism in the left hippocampus with no hypofrontality. Safety and efficacy of clozapine in this age group is suggested by an open trial in eight subjects and a double-blind haloperidol/clozapine comparison in seven subjects. In a double-blind comparison of desipramine and placebo, children with autistic (n=24) disorder show a selective response to clomipramine supporting a serotonergic disturbance in this disorder.